Application of dynamic contrast enhanced ultrasound analysis in predicting early response to systemic therapy of intrahepatic cholangiocarcinoma.

OBJECTIVE: To evaluate the value of dynamic contrast-enhanced ultrasound (DCE-US) analysis in early prediction of tumor response to systemic treatment in patients with intrahepatic cholangiocarcinoma (ICC). PATIENTS & METHODS: In this retrospective study, patients diagnosed with ICC by core needle biopsy and histopathological results were included. All patients were diagnosed as advanced stages (stage III/IV) by the 8th edition of the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) TNM staging system. Liver contrast-enhanced ultrasound (CEUS) examination, DCE-US analysis, CT/MRI, and blood tests were performed in all patients before and 2 months after systemic treatment. CEUS procedure was performed using an ultrasound system (ACUSON Sequoia; Siemens Medical Solutions, Germany) equipped with a 5C1 MHz convex array transducer. Time-intensity curves (TIC) and quantitative parameters were created with VueBox software. According to one-year results of the modified Response Evaluation Criteria in Solid Tumors (m-RECIST) based on CT/MRI, patients were divided into the responder group (RG) and the non-responder group (NRG). Before and 2 months after systemic therapy, the DCE-US perfusion parameters was compared using the paired-sample t test and the Wilcoxon test. RESULTS: From September 2020 to December 2021, a total of 24 patients diagnosed with advanced ICC were included (11 males, 13 females, mean age 59.4 ± 1.8 years). According to the one year of m-RECIST results, 17 cases (70.8 %) were classified as non-responders by the final m-RECIST criteria, while 7 cases (19.2 %) were responders. Comparing before and 2 months after therapy, the RG took longer time to reach peak intensity, and the peak intensity of TIC was lower. While the TICs of NRG revealed faster enhancement after therapy. Among all DCE-US quantitative parameters, PE (peak enhancement), WiR (wash-in rate), WiPI (wash-in perfusion index) and WoR (wash-out rate) reduced significantly following 2 months of systemic therapy in RG (P < 0.05). Comparing to RG, PE and WiPI decreased slightly 2 months after therapy in NRG (P < 0.05). CONCLUSIONS: The DCE-US analysis with quantitative parameters has the potential value to make early and quantitative evaluation of treatment response to systemic therapy in ICC patients.

Bioactivities and Action Mechanisms of Ellipticine Derivatives Reported Prior to 2023.

Currently, natural products are one of the priceless options for finding novel chemical pharmaceutical entities. Ellipticine is a naturally occurring alkaloid isolated from the leaves of Ochrosia elliptica Labill. Ellipticine and its derivatives are characterized by multiple biological activities. The purpose of this review was to provide a critical and systematic assessment of ellipticine and its derivatives as bioactive molecules over the last 60 years. Publications focused mainly on the total synthesis of alkaloids of this type without any evaluation of bioactivity have been excluded. We have reviewed papers dealing with the synthesis, bioactivity evaluation and mechanism of action of ellipticine and its derivatives. It was found that ellipticine and its derivatives showed cytotoxicity, antimicrobial ability, and anti-inflammatory activity, among which cytotoxicity toward cancer cell lines was the most investigated aspect. The inhibition of DNA topoisomerase II was the most relevant mechanism for cytotoxicity. The PI3K/AKT pathway, p53 pathway, and MAPK pathway were also closely related to the antiproliferative ability of these compounds. In addition, the structure-activity relationship was deduced, and future prospects were outlined. We are confident that these findings will lay a scientific foundation for ellipticine-based drug development, especially for anticancer agents.

Normal value of virtual touch imaging quantification elastography in measurements of pancreas.

OBJECTIVE: To evaluate pancreatic tissue stiffness and provide a normal reference shear wave velocity (SWV) value of pancreas from healthy adults by Virtual Touch Imaging Quantification (VTIQ) measurements. METHODS: Healthy adult volunteers without known history of hepatobiliary or pancreatic diseases were included. VTIQ elastography (Siemens ACUSON Sequoia, 5C-1 transducer) was used. SWV values were measured at the cephalic, corpus and tail of pancreas and replicated different operators' obtained data. Subgroups were classified according to the volunteers' gender, age, body mass index (BMI), depth of measurements and the echogenicity of the pancreas. RESULTS: From February 2023 to July 2023, 33 healthy adult volunteers were included. The success rate of VTIQ measurements in cephalic, corpus and tail regions was 90.90 % (30/33), 96.97 % (32/33) and 90.90 % (30/33) respectively. The color elastograms of healthy adult pancreas showed uniform blue or simultaneously blue and green. The average SWV values were 0.97±0.26 m/s for cephalic, 0.91±0.24 m/s for corpus and 0.97±0.25 m/s for pancreatic tail respectively (P = 0.198). The mean SWV values of pancreas did not show significant difference with age, gender or depth (P > 0.05). BMI was an influence factor in the measurements of SWV values of cephalic and tail of pancreas (P < 0.05). Pancreas with hyperechoic parenchyma showed higher mean SWV values (P < 0.05). The intra-observer (ICC = 0.938 [95% CI: 0.869-0.971]) and the inter-observer (ICC = 0.887 [95% CI: 0.760-0.947]) agreements of VTIQ measurements were excellent. CONCLUSIONS: The mean SWV value of the pancreas in healthy adults was 0.96±0.20 m/s (range: 0.52-1.74 m/s). VTIQ technique can be used in pancreatic stiffness measurements with good reliability.

Hepatic steatosis using ultrasound-derived fat fraction: First technical and clinical evaluation.

OBJECTIVES: To explore the technical and clinical evaluation of ultrasound-derived fat fraction (UDFF) measurement in adult patients in whom fatty liver was suspected. MATERIALS AND METHODS: In this prospective study, 41 participants were initially enrolled in our hospital between October 2022 and December 2022 and received UDFF assessment using Siemens ACUSON Sequoia system equipped with DAX transducer. UDFF measurement was performed three times to obtain UDFF values from each imaging location (V hepatic segment and VIII hepatic segment) per participant, and the depth (skin-to-capsule distance) was automatically measured. The echogenicity of liver tissue in B mode ultrasound (BMUS) was compared to the normal kidney tissue, and fatty liver was graded as mild (Grade 1), moderate (Grade 2), and severe (Grade 3). The median of the acquired overall median UDFF values was used for statistical analysis. All ultrasound examinations were performed by one of two radiologists (with 20 and 10 years of liver ultrasound imaging experience). RESULTS: Finally, UDFF measurement was successfully performed on 38 participants to obtain valid values, including 21 men with a median age of 40.0 years (interquartile range [IQR]: 23.0 - 58.5) and 17 women with a median age of 60.0 years (IQR: 29.5 - 67.0). Fatty liver was diagnosed by BMUS features in 47.4% (18/38) participants. Among all participants, the median UDFF value was 7.0% (IQR: 4.0 - 15.6). A significant difference in UDFF values was found between participants with fatty liver and without fatty liver (U = 7.0, P < 0.001), and UDFF values elevated as the grade of the fatty liver increased (P < 0.001). The median UDFF values from the three UDFF measurements obtained during each ultrasound examination showed excellent agreement (ICC = 0.882 [95% confidence interval: 0.833 - 0.919]). The Spearman correlation of UDFF values in different depths was moderate, with a rs value of 0.546 (P < 0.001). No significant differences in UDFF values were found between V hepatic segment and VIII hepatic segment (U = 684.5, P = 0.697). CONCLUSIONS: UDFF provides a novel non-invasive imaging tool for hepatic steatosis assessment with excellent feasibility.

[Spatial Network of Urban Heat Environment in Beijing-Tianjin-Hebei Urban Agglomeration Based on MSPA and Circuit Theory].

Rapid urbanization has increased the complexity of the urban heat environment system, which has negative impacts on the health of the urban ecological system and the human habitat. By combining theories and technologies such as geographic information systems, remote sensing, morphological spatial pattern analysis, and circuit theory with data from MODIS land surface temperature production, urban heat island patches in the Beijing-Tianjin-Hebei urban agglomeration were quantitatively identified in terms of their spatial and temporal distribution characteristics and their spatial and temporal transfer paths. This foundation revealed the geographical network structure of the urban heat environment as well as the spatial and temporal evolution process of critical corridors. According to the findings, urban heat island patches covered 16610 km2 in 2020, accounting for 7.68% of the study area. In the Beijing-Tianjin-Hebei urban agglomeration, both the area and the number of urban heat island patches considerably increased between 2005 and 2020, going from being dominated by isolated island types of urban heat island patches in 2005 to being dominated by core types in 2020. In particular, the non-urban heat island patches, core type, and edge type of urban heat island patches in 2005 were the major ancestors of the core type and edge type urban heat island patches in 2020. In the Beijing-Tianjin-Hebei urban agglomeration, there were more urban heat environment source sites, corridor length, densities, and present densities in 2020 than there were in 2005. The sensitive corridor was found to be the predominant type of urban heat island corridor in the Beijing-Tianjin-Hebei urban agglomeration in 2020. The number of sensitive corridors increased the highest in the period from 2005-2020. As the coefficient of urban heat environment corridors increased concurrently, it was apparent that the urban heat environment corridor had a propensity to grow continuously in the Beijing-Tianjin-Hebei urban agglomeration. The active adaptation and mitigation measures of the urban heat environment were proposed, and a spatial network model of the urban heat environment was finally provided. To adapt to, mitigate, and promote urban sustainable development risks, these research findings will serve as a paradigm for the identification of the urban heat environment spatial network actively and methodically.

Spatial and temporal variations of soil nutrients of cropland in Northeast China from the 1980s to the 2010s.

In recent years, the degradation of cropland soils in Northeast China, such as "thinned, barren, and hardened", has become increasingly serious, with consequences on sustainable development of agriculture. Based on the data from Soil Types of China (1980s) and Soil Series of China (2010s), we examined the change patterns of soil nutrient conditions across different regions and soil types in Northeast China over the past 30 years through the statistical analysis of large samples. The results showed that: 1) from the 1980s to the 2010s, soil nutrient indicators in Northeast China changed to different degrees. Soil pH decreased by 0.03. Soil organic matter (SOM) content decreasd most prominently, by 8.99 g·kg-1 or 23.6%. Soil total N (TN), total P (TP) and total K (TK) contents showed increasing trends, with increases of 17.1%, 46.8%, and 4.9%, respectively. 2) Changes in soil nutrient indicators differed across different provinces and cities. Soil acidification in Liaoning was the most obvious, with pH decreasing by 0.32. SOM content in Liaoning decreased most significantly, by 31.0%. Soil TN, TP, and TK contents in Liaoning increased most significantly by 73.8%, 248.1% and 44.0%, respectively. 3) The changes of soil nutrients varied greatly among soil types, with brown soil and kastanozems showing the greatest decrease in pH. The SOM content of all soil types showed a decreasing trend, with 35.4%, 33.8% and 26.0% reduction in brown soil, dark brown forest soil and chernozem respectively. The greatest increase in TN, TP and TK contents were observed in brown soil by 89.1%, 232.8%, and 48.5%, respectively. In summary, declining organic matter content and soil acidification were the core problems of soil degradation in Northeast China from the 1980s to the 2010s. Reasonable tillage methods and targeted conservation strategies are critically needed to ensure the sustai-nable development of agriculture in Northeast China.

Synthesis, biological activity and mechanism of action of novel allosecurinine derivatives as potential antitumor agents.

Cancer with low survival rates is the second main cause of death among all diseases in the world and consequently, effective antineoplastic agents are urgently needed. Allosecurinine is a plant-derived indolicidine securinega alkaloid shown bioactivity. The object of this study is to investigate synthetic allosecurinine derivatives with considerable anticancer capacity against nine human cancer cell lines as well as mechanism of action. We synthesized twenty-three novel allosecurinine derivatives and evaluated their antitumor activity against nine cancer cell lines for 72 h by MTT and CCK8 assays. FCM was applied to analyze the apoptosis, mitochondrial membrane potential, DNA content, ROS production, CD11b expression. Western blot was selected to analyze the protein expression. Structure-activity relationships were established and potential anticancer lead BA-3 which induced differentiation of leukemia cells towards granulocytosis at low concentration and apoptosis at high concentration was identified. Mechanism studies showed that mitochondrial pathway mediated apoptosis within cancer cells with cell cycle blocking was induced by BA-3. In addition, western blot assays revealed that BA-3 induced expression of the proapoptotic factor Bax, p21 and reduced the levels of antiapoptotic protein such as Bcl-2, XIAP, YAP1, PARP, STAT3, p-STAT3, and c-Myc. Collectively, BA-3 was a lead compound for oncotherapy at least in part, through the STAT3 pathway. These results were an important step in further studies on allosecurinine-based antitumor agent development.

Component-target network and mechanism of Qufeng Zhitong capsule in the treatment of neuropathic pain.

ETHNOPHARMACOLOGICAL RELEVANCE: Qufeng Zhitong capsule (QFZTC) is a traditional Chinese medicine (TCM) clinically used for treating pain. However, the active ingredients of QFZTC and its pharmacological mechanism in the treatment of neuropathic pain (NP) remain unclear. AIM OF THE STUDY: We aimed to identify the active ingredients of QFZTC and reveal its target genes and underlying mechanism of action in NP. MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) was used to identify the active ingredients of QFZTC. Network pharmacology analysis was conducted to determine the core targets and pathway enrichment of QFZTC. An NP mice model was established through chronic compression injury (CCI) surgery of the sciatic nerve, while von Frey instrumentation and a thermal stimulator were employed to measure the sensitivity of mice to mechanical and thermal stimuli. Immunofluorescence was used to observe the expression of TLR4 and p-P65 in microglia. Western blotting was used to detect the levels of protein expression of Iba-1, TLR4, MyD88, P65, p-P65, and c-Fos, while ELISA kits were used to detect the release of TNF-α, IL-6, and IL-1ß. RESULTS: Seven active ingredients were identified in QFZTC: gallic acid, loganylic acid, syringin, corilagin, loganin, ellagic acid, and osthole. Network analysis identified TLR4, TNF, IL6, IL1ß, and c-Fos as core targets, and Toll-like receptors and NF-κB as core signaling pathways. Treatment with QFZTC significantly relieved mechanical allodynia and thermal hyperalgesia in CCI mice models. CCI induced an increase in the expression of TLR4 and p-P65 in microglia, whereas QFZTC dose-dependently reduced the expression of Iba-1, TLR4, MyD88, and p-P65 in the spinal cord. QFZTC inhibited the expression of the c-Fos pain marker and reduced the expression of the TNF-α, IL-6, and IL-1ß inflammatory factors. CONCLUSION: We combined the active ingredients of QFZTC with network pharmacology research to clarify its biological mechanism in the treatment of NP. We demonstrated that QFZTC reduced NP in mice probably through regulating the spinal microglia via the TLR4/MyD88/NF-κB signaling pathway. Hence, QFZTC could be regarded as a potential drug for relieving NP.

[Research on suitable distribution of Paris yunnanensis based on remote sensing and GIS].

Paris yunnanensis is a kind of rare medicinal herb, having a very high medicinal value. Studying its suitable ecological condition can provide a basis for its rational exploitation, artificial cultivation, and sustainable utilization. A practicable method in this paper has been proposed to research the suitable regional distribution of P. yunnanensis in Sichuan province. By the case study of P. yunnanensis in Sichuan province, and according to related literatures, the suitable ecological condition of P. yunnanensis such as altitude, mean annual temperature (MAT), annual precipitation, regional slope, slope ranges, vegetative cover, and soil types was analyzed following remote sensing (RS) and GIS.The appropriate distribution regionof P. yunnanensis and its area were extracted based on RS and GIS technology,combing with the information of the field validation data. The results showed that the concentrated distribution regions in counties of Sichuan province were, Liangshan prefecture, Aba prefecture, Sertar county of Ganzi prefecture, Panzhihua city, Ya'an city, Chengdu city, Meishan city, Leshan city, Yibin city, Neijiang city, Luzhou city, Bazhong city, Nanchong city, Guangyuan city and other cities and counties area.The suitable distribution area in Sichuan is about 7 338 km², accounting for 3.02% of the total study regional area. The analysis result has high consistency with the filed validation data, and the research method for P. yunnanensis distribution region based onspatial overlay analysis and the extracted the information of land usage and ecological factors following the RS and GIS is reliable.

[Application of remote sensing and GIS in study of suitability distribution of Swertia mussotii, a Tibetan medicine in Sichuan province].

Swertia mussotii is a kind of rare medicinal materials, the relevant researches are mainly concentrated on its medicinal efficacy and medicinal value till now, researches of adaptive distribution by applying remote sensing and GIS are relatively less. This study is to analyze the adaptive distribution of S.mussotii in Sichuan province by applying remote sensing and GIS technology, and provide scientific basis for the protection and development of wild resources, artificial cultivation and adjustment of Chinese medicine industrial distribution in Sichuan province. Based on literature review and ecological factors such as altitude, annual precipitation and annual average temperature, this study extracted ecological factors, overlay analysis in GIS, as well as combining GPS field validation data by means of remote sensing and GIS, discusses the adaptive distribution of SMF sin Sichuan province. ①The area of adaptive distribution of S. mussotii in Sichuan province is 1 543.749 km², mainly in Dege county, Ganzi county, Daofu county, Kangding county, Barkam, Jinchuan county, Xiaojin county, Danba county, Daocheng county, Xiangcheng county, Xinlong county, Aba county, Muli county and other counties and cities, accounts for about 7.25% in total area. ② Combining statistical information and field validation, this study found that S. mussotii adaptive distribution gained by remote sensing and GIS is in conformity with its actual distribution. The study shows that remote sensing and GIS technology are feasible to obtain the S. mussotii adaptive distribution, they can further be applied to studies on adaptive distributions of other rare Chinese medicinal herb.

Differential gene expression profiles between two subtypes of ischemic stroke with blood stasis syndromes.

Ischemic stroke is a cerebrovascular thrombotic disease with high morbidity and mortality. Qi deficiency blood stasis (QDBS) and Yin deficiency blood stasis (YDBS) are the two major subtypes of ischemic stroke according to the theories of traditional Chinese medicine. This study was conducted to distinguish these two syndromes at transcriptomics level and explore the underlying mechanisms. Male rats were randomly divided into three groups: sham group, QDBS/MCAO group and YDBS/MCAO group. Morphological changes were assessed after 24 h of reperfusion. Microarray analysis with circulating mRNA was then performed to identify differential gene expression profile, gene ontology and pathway enrichment analyses were carried out to predict the gene function, gene co-expression and pathway networks were constructed to identify the hub biomarkers, which were further validated by western blotting and Tunel staining analysis. Three subsets of dysregulated genes were acquired, including 445 QDBS-specific genes, 490 YDBS-specific genes and 1676 blood stasis common genes. Our work reveals for the first time that T cell receptor, MAPK and apoptosis pathway were identified as the hub pathways based on the pathway networks, while Nfκb1, Egfr and Casp3 were recognized as the hub genes by co-expression networks. This research helps contribute to a clearer understanding of the pathological characteristics of ischemic stroke with QDBS and YDBS syndrome, the proposed biomarkers might provide insight into the accurate diagnose and proper treatment for ischemic stroke with blood stasis syndrome.

[Study on suitable distribution areas of Grifola umbellate in Sichuan province based on remote sensing and GIS].

Grifola umbellate is the important medicinal materials in China which has a very high medicinal value. This study analyzedthe suitable distribution areasof G. umbellate and provided scientific basis for determining G. umbellate planting regions and planning production distribution reasonably. The suitable distribution areas of G. umbellate in Sichuan province was researched based on TM, ETM+, and DEM data,the key ecological factors that affect the growth of G. umbellate were extracted, including elevation, slope, aspect, average annual temperature,average annual precipitation,forest information,soil information, following remote sensing and GIS techniques, combining field researchdata. The results showed that the G. umbellate resources in Sichuan province were mainly distributed in Pingwu, Beichuan, Licountry, Yanyuan, Xichang, Dechang, Yanbian, Miyi, Huidong, Panzhihua and so on, the suitability distribution areas is 276.214 4 km² approximately and accounting for more than 0.143 3% of the total area.According to the related document information and the field investigation, showed that the suitability distribution based on RS and GIS were corresponded with the actual distribution areas of G. umbellate.

Study on suitable distribution areas of Notopterygium incisum in Sichuan province based on remote sensing and GIS.

Notopterygium incisum is the important medicinal materials of the Tibetan-Qiang medical system in China, also one of the rare and endangered medicinal materials in the Plateau areas in the meantime. Taking the planting of in Sichuan province as an example, research on the N. incisum in Sichuan utilize remote sensing and GIS techniques, bind growth environment factor, including height factor, average annual precipitation, average annual temperature, forest information, were chosen according to habitat conditions. And combine field measurement to verify. The results indicate that N. incisum resources in Sichuan province were mainly distributed in the alpine valley and the northwest of the plateau, which suitability distribution areas of 4145 km2 approximately and accounting for 2% of the total area. Suitability areas accounting for more than 2% of the respective total area in Heishui county, Lixian county, Xiaojin county, Kangding county, ect. According to the field investigation and the related document information record, drawn that the suitability distribution based on RS and GIS were corresponded with the actual distribution areas of N. incisum resources. It's feasible to divide the suitability distribution area of N. incisum using RS and GIS, which will provide a scientific basis for a comprehensive investigation of the distribution as well as its rational exploitation and protection.

Assessment of effects of climate change and grazing activity on grassland yield in the Three Rivers Headwaters Region of Qinghai-Tibet Plateau, China.

Inter-annual dynamics of grassland yield of the Three Rivers Headwaters Region of Qinghai-Tibet Plateau of China in 1988-2005 was analyzed using the GLO-PEM model, and the herbage supply function was evaluated. The results indicate that while grassland yield in the region showed marked inter-annual fluctuation there was a trend of increased yield over the 18 years of the study. This increase was especially marked for Alpine Desert and Alpine Steppe and in the west of the region. The inter-annual coefficient of variation of productivity increased from the east to the west of the region and from Marsh, Alpine Meadow, Alpine Steppe, Temperate Steppe to Alpine Desert grasslands. Climate change, particularly increased temperatures in the region during the study period, is suggested to be the main cause of increased grassland yield. However, reduced grazing pressure and changes to the seasonal pattern of grazing could also have influenced the grassland yield trend. These findings indicate the importance of understanding the function of the grassland ecosystems in the region and the effect of climate change on them especially in regard to their use to supply forage for animal production. Reduction of grazing pressure, especially during winter, is indicated to be critical for the restoration and sustainable use of grassland ecosystems in the region.

Copper(II)-mediated resolution of alpha-halo carboxylic acids with chiral O,O'-dibenzoyltartaric acid: spontaneous racemization and crystallization-induced dynamic resolution.

Herein we present a new example of coordination-mediated resolution of racemic acids by a chiral acid. The reaction of copper(II) acetate monohydrate, optically pure O,O'-dibenzoyltartaric acid (DBTA) and racemic alpha-bromo-2-chlorophenylacetic acid (HL1) in acetonitrile solution afforded a binuclear copper(II) complex with D-DBTA dianion, alpha-bromo-2-chlorophenylacetate and acetate as ligands. After decomposition of the complex with acid, the optically active acid ((R)-HL1) was obtained. Similarly, alpha-bromo-2-fluorophenylacetic acid (HL2), alpha-bromo-2-bromophenylacetic acid (HL3), alpha-chloro-2-chlorophenylacetic acid (HL4), alpha-chloro-2-fluorophenylacetic acid (HL5), alpha-bromophenylacetic acid (HL6), alpha-bromo-4-chlorophenylacetic acid (HL7), 2-bromopropionic acid (HL8) and 2-chloropropionic acid (HL9) were resolved by the same method. Satisfactory results were obtained for HL2 to HL5. For HL6 and HL7, only racemic acids were obtained. For the two alpha-halo aliphatic acids (HL8 and HL9), poor enantioselectivity was obtained. It is more interesting that three acids (HL1, HL2 and HL3) could spontaneously racemize in acetonitrile solution, which resulted in crystallization-induced dynamic resolution (CIDR) with greater than 50% yield.